Pathological fracture of the femur is a common and serious consequence of metastatic cancer of the breast, lung, prostate, kidney and thyroid. Surgical fixation is used to prevent pathological fracture when a patient is thought to be at high risk of fracture. However, current methods for identifying patients in need of fixation involve only simple rules of thumb, such as destruction of more than 50% of the cortex, or diameter greater than 2.5 cm, and have been shown to be inadequate. To address this issue, this study will explore the feasibility of using a new imaging/computational technique for assessing the risk of pathological fracture of the femur. This technique will employ automatically generated, computed tomographic (CT) scan-based finite element (FE) models to estimate the strength (fracture loads) of proximal femora and femoral shafts with metastatic lesions. This will be the first study in which FE modeling has been used to compute fracture loads for bones with actual metastatic tumors. Specific Aims of this study are to evaluate the accuracy and precision of this automated CT/FE technique, in the context of tumor-involved bones, by computing and measuring fracture loads in vitro for: (a) eight femoral shafts with metastatic lesions tested in four-point bending; (b) eight femoral shafts with metastatic lesions tested in torsion; and (c) ten proximal femora with metastatic lesions under joint loading similar to that during single-limb stance. If this new imaging/ computational technique successfully predicts fracture loads of femora with metastatic lesions, the next step would be to relate the CT/FE-computed fracture loads to fracture risk. The long-term goal will be to implement this technique in the clinical setting so that the incidence of both pathological fracture and unnecessary prophylactic fixation can be reduced, with a concomitant reduction in health care costs. It is suggested (by the applicant) that this CT/FE technique would also be useful for basic science research to help better understand the interaction of bone mechanics, tumors and bone response.